Many cellular processes are driven by molecular motors, specialized proteins that utilize the energy generated from chemical reactions to perform physical work. Molecular motors play key roles in, for example, muscle contraction, protein degradation and recycling, cargo transport, and cell motility. Defects in motor function are implicated broadly in cancer, as well as numerous cardiovascular, neurological, and reproductive diseases. Researchers in the Theoretical and Computational Biophysics Group are interested in studying the complex conformational transitions that underlie the chemo-mechanical action of molecular motors toward characterizing their mechanisms and relationships to human disease.

Spotlight: Waste Recycler of the Cell (Jun 2016)


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While waste recycling became popular in our daily life, living cells mastered waste recycling of their protein content since their very beginning. Recycling of unneeded protein molecules in cells is performed by a molecular machine called 26S proteasome, which cuts these proteins into smaller pieces and releases the pieces into the cell interior for reuse as building blocks for new protein. Proteins that need to be recycled are usually those that are misfolded. Proteins are recognized as such by the cells' so-called quality control system. This system labels misfolded proteins by a tag made of tetra-ubiquitin protein chains. The 26S proteasome machine recognizes and binds to these tags via its subunit Rpn10. After Rpn10 binds to the tetra-ubiquitin tag and pulls the protein close, the 26S proteasome unwinds the tagged protein and cuts it into pieces. A recent study, based on molecular dynamics simulations with NAMD, sheds light onto how 26S proteasome and Rpn10 recognize the tetra-ubiquitin tag in three stages: In stage 1 of the recognition process conserved complementary electrostatic patterns of Rpn10 and ubiquitins guide protein association; stage 2 induces refolding of Rpn10 and tetra-ubiquitin tag; stage 3 facilitates formation of hydrophobic contacts between the tag and Rpn10. More information is available on our 26S proteasome website.

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Publications Database
  • The structure of the human 26S proteasome at a resolution of 3.9 Å. Andreas Schweitzer, Antje Aufderheide, Till Rudack, Florian Beck, Gunter Pfeifer, Jurgen M. Plitzko, Eri Sakata, Klaus Schulten, Friedrich Forster, and Wolfgang Baumeister. Proceedings of the National Academy of Sciences, USA, 113:7816-7821, 2016.
  • Recognition of poly-ubiquitins by the proteasome through protein re-folding guided by electrostatic and hydrophobic interactions. Yi Zhang, Lela Vukovic, Till Rudack, Wei Han, and Klaus Schulten. Journal of Physical Chemistry B, 120:8137-8146, 2016.
  • Molecular mechanism of processive 3' to 5' RNA translocation in the active subunit of the RNA exosome complex. Lela Vukovic, Christophe Chipot, Debora L. Makino, Elena Conti, and Klaus Schulten. Journal of the American Chemical Society, 138:4069-4078, 2016.
  • Mechanism of substrate translocation by a ring-shaped ATPase motor at millisecond resolution. Wen Ma and Klaus Schulten. Journal of the American Chemical Society, 137:3031-3040, 2015.
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    General Medical Sciences
    of the National Institutes
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